Frontal osteitis complicated with bone necrosis is rare.In addition,the condition has various etiologies,such as frontal sinusitis,penetrating head injury,postoperative complications after sinus surgery,and hematogeno...Frontal osteitis complicated with bone necrosis is rare.In addition,the condition has various etiologies,such as frontal sinusitis,penetrating head injury,postoperative complications after sinus surgery,and hematogenous spread from distant sites.In frontal osteitis,early diagnosis is important,and fistulization of pus in the scalp or on the traumatized forehead may raise the suspicion of osteitis in one of the skull bones.The exclusion of osteonecrosis is such cases is an emergency;hence,a magnetic resonance imaging and a computed tomography scan are required in the absence of skull radiography.Early administration of the appropriate treatment in the immediate post-trauma period ensures effective prevention of frontal osteitis;however,the treatment of bone necrosis involves debridement and antibiotic therapy to prevent fatal intracranial complications.This report presents the case of a 16-year-old female patient who experienced sexual and physical assault that resulted in undetected frontal trauma complicated with frontal osteonecrosis.Thorough clinical examination of the patient was performed,and follow-up and multidisciplinary management enabled the social integration of the patient.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infect...BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.展开更多
BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identi...BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.展开更多
BACKGROUND Although acute pancreatitis and walled-off necrosis(WON)are rare complications following aortic surgery,they are serious risk factors for postoperative mortality.Considering the poor general condition of th...BACKGROUND Although acute pancreatitis and walled-off necrosis(WON)are rare complications following aortic surgery,they are serious risk factors for postoperative mortality.Considering the poor general condition of the postoperative patient,more effective and less invasive treatments are favorable.CASE SUMMARY A 67-year-old man was referred to our hospital for the treatment of WON after acute pancreatitis.He had undergone total aortic arch replacement due to aortic arch aneurysm and coronary artery bypass grafting due to angina pectoris 6 weeks prior in another hospital.On the second postoperative day,laboratory data and computed tomography showed that the patient had developed acute pancreatitis.Although conservative management(antibiotics,hydration,etc.)had helped in relieving the symptoms of acute pancreatitis,peripancreatic fluid collection(PFC)persisted,accompanied by duodenal obstruction and vomiting.Contrastenhanced computed tomography showed that the heterogeneous enhancement and fluid collection in the pancreatic body and tail had increased,consistent with walled-off WON.We therefore performed endoscopic ultrasound-guided transluminal drainage for the PFC.As a result,the WON resolved gradually,resulting in improved oral intake.CONCLUSION Acute pancreatitis is a rare gastrointestinal complication following thoracic and thoracoabdominal aortic aneurysm surgery.To the best of our knowledge,this is the first case of WON after aortic arch surgery treated with endoscopic ultrasound-guided transluminal drainage for PFC.展开更多
Background:Infected pancreatic necrosis(IPN)is a highly morbid local complication following necrotizing pancreatitis.Early enteral nutrition has been proven to be effective in preventing IPN.This study aimed to assess...Background:Infected pancreatic necrosis(IPN)is a highly morbid local complication following necrotizing pancreatitis.Early enteral nutrition has been proven to be effective in preventing IPN.This study aimed to assess the association between the trajectory of prealbumin(PAB)during the early phase of acute pancreatitis(AP)and the incidence of IPN and other clinical outcomes.Methods:This retrospective,dual-centered study screened patients with AP admitted to the Center of Acute Pancreatitis,Jinling Hospital and the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2022.The PAB levels during the first week after admission were collected.The primary outcome was the incidence of IPN within 90 days after AP onset.Group-based trajectory modelling was performed to describe the trajectory of PAB levels over time.A Cox proportional hazard model was used to facilitate the interpretation of the time-varying hazard ratio(HR)between PAB and outcomes.Fine-Gray sub-distribution hazard model was adopted for sensitivity analysis.Results:A total of 373 patients were included,of whom 82(22.0%)were diagnosed with IPN within 90 days.The trajectory model assigned 232 patients to the low-level PAB(L-PAB)group and 141 to the high-level PAB(H-PAB)group.The incidence of 90-day IPN in the L-PAB group was significantly higher than that in the H-PAB group(26.7%vs.14.2%,P=0.005).The multivariate Cox regression model showed that a high PAB trajectory was associated with a lower incidence of IPN(HR=0.52,95%CI:0.30-0.89;P=0.017)after adjustment for potential confounders.In the sensitivity analysis,taking death as a com-peting risk,high PAB trajectory remained significantly associated with a lower incidence of IPN in the Fine-Gray model(HR=0.55,95%CI:0.33-0.92;P=0.022).Conclusions:A high PAB trajectory within the first week of AP was significantly associated with a lower incidence of IPN within 90 days after AP onset.Dynamic monitoring of PAB levels in the early phase of AP may play an important role in stratifying patients at high risk of developing IPN.展开更多
Laparoscopic sleeve gastrectomy(LSG),as an effective treatment for morbid obesity and its metabolic complications,exerts its therapeutic effects by significantly reducing body weight and improving metabolic disorders....Laparoscopic sleeve gastrectomy(LSG),as an effective treatment for morbid obesity and its metabolic complications,exerts its therapeutic effects by significantly reducing body weight and improving metabolic disorders.Its core mechanisms involve multi-level regulation of free fatty acid(FFA)metabolism and chronic low-grade inflammatory states(represented by tumor necrosis factor-alpha,TNF-α).This paper systematically reviews the direct impact of LSG on FFA dynamics including lipolysis,tissue uptake,and oxidation,as well as the molecular pathways through which it indirectly regulates TNF-αby reducing adipose tissue inflammation,improving intestinal barrier function,and modulating epigenetic modifications such as SCD gene methylation.Postoperatively,FFA and TNF-αform a bidirectional promoting feedback loop.LSG effectively breaks this vicious cycle of mutual promotion between the two under obese conditions by reducing FFA levels and inhibiting TNF-αexpression.Lower FFA levels alleviate inflammatory signal activation,while reduced TNF-αinhibits lipolysis,collectively promoting the restoration of insulin sensitivity.A thorough understanding of these mechanisms provides a theoretical basis for optimizing surgical strategies and developing targeted therapies.展开更多
BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-Eu...BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.展开更多
BACKGROUND Irreversible transmural intestinal necrosis(ITIN)is associated with high mortality rates in patients with acute occlusive mesenteric ischemia(AOMI).Currently,there are not many studies on the use of dual en...BACKGROUND Irreversible transmural intestinal necrosis(ITIN)is associated with high mortality rates in patients with acute occlusive mesenteric ischemia(AOMI).Currently,there are not many studies on the use of dual energy computed tomography(DECT)for evaluating ITIN.AIM To evaluate the diagnostic value of DECT for ITIN in AOMI.METHODS The cases and computed tomography(CT)images of 102 patients with clinically diagnosed AOMI(including 48 ITIN)from January 2012 to January 2022 were retrospectively collected.The CT scans included both multidetector CT and DECT.The raw data from DECT portal-venous phase were reconstructed into 120 kVp mixed energy image,50 keV virtual monoenergetic imaging,and iodine map.Two radiologists independently completed the subjective visual assessment of CT signs related to AOMI.Objective parameters,including the attenuation of the normal and_(lesion)intestinal wall segment(CT50 keV_(lesion),CT_(50 keV normal/lesion))and iodine concentrations(IC_(lesion)and I_(Cnormal/lesion)),were quantified.Furthermore,multivariate logistic regression,receiver operating characteristic curves,and area under the curve(AUC)values were used to evaluate the subjective and objective indicators in predicting ITIN.RESULTS Regarding subjective signs,logistic regression analysis revealed reduced or absent bowel wall enhancement[odds ratio(OR)=5.576,95%confidence interval(CI):1.547-20.093],bowel dilation(OR=11.613,95%CI:3.790-35.586),and parenchymatous organ infarction(OR=4.727,95%CI:1.536-14.551)were independent risk factors for the ITIN.CT subjective signs had a high diagnostic efficacy for ITIN(AUC=0.853).The two DECT objective parameters also exhibited excellent diagnostic value for ITIN,with an AUC of 0.79,a cut-off value of CT50 keV normal/_(lesion)=2.81,and an AUC of 0.777 with a cut-off value of I_(Cnormal/lesion)=2.39.The Delong test showed that there was no significant difference in the efficacy of subjective CT signs and objective DECT parameters(P>0.05).Importantly,we observed that I_(Cnormal/lesion)combined with subjective signs(bowel dilation and parenchymatous organ infarction)had the highest predictive performance(AUC=0.894),sensitivity(100%),and specificity(70.83%),which was statistically different from the AUC of CT subjective signs(P=0.017).CONCLUSION I_(Cnormal/lesion)(DECT-based features)combined with CT subjective signs(bowel dilatation and parenchymatous organ infarction)showed favorable predictive performance for ITIN in AOMI,which may help clinicians develop timely treatment strategies.展开更多
The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated ...The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated that GC exacerbates the oxidative stress(OS)microenvironment via promoting nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)expression in human,rat,and mesenchymal stem cells(MSCs)samples,thus generating excessive reactive oxygen species(ROS),leading to increased apoptosis and unbalanced osteolipogenic differentiation.Furthermore,computational docking results revealed that AMY could bind specifically to the predicted binding sites of NOX4.Additionally,AMY ameliorated the OS microenvironment of MSCs via decreasing NOX4 expression and inhibiting NOX4/ROS/p38MAPK signaling,thereby reversing the GC-induced apoptosis and imbalanced osteolipogenic differentiation,and ultimately alleviating GANFH.In summary,we demonstrated for the first time that AMY attenuated apoptosis and maintained osteolipogenic differentiation balance in MSCs via specifically targeting NOX4,inhibiting NOX4/ROS/p38MAPK signaling,thereby treating GANFH.展开更多
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have...Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.展开更多
Approximately 20%-30%of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis(IPN),a highly morbid and potentially lethal complication.Early identification of patients at high risk of IPN m...Approximately 20%-30%of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis(IPN),a highly morbid and potentially lethal complication.Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes.In the past two decades,several markers and predictive tools have been proposed and evaluated for this purpose.Conventional biomarkers like C-reactive protein,procalcitonin,lymphocyte count,interleukin-6,and interleukin-8,and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN.On the other hand,scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested,and the results showed that they may provide better accuracy.For early prevention of IPN,several new therapies were tested,including early enteral nutrition,anti-biotics,probiotics,immune enhancement,etc.,but the results varied.Taken together,several evidence-supported predictive markers and scoring systems are readily available for predicting IPN.However,effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition.In this editorial,we summarize evidence concerning early prediction and prevention of IPN,providing insights into future practice and study design.A more homo-geneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN,thereby achieving individualized treatment.展开更多
OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-...OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.METHODS:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays.The morphology of cancer cells was observed with inverted phase contrast microscope.The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays.The expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting assay.RESULTS:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells.The synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.CONCLUSION:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.展开更多
Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of...Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.展开更多
BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with ...BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.展开更多
BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A...BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.展开更多
BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be u...BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be used to assess the type of AKI and the severity of the disease.We performed a systematic review with metaanalysis to evaluate the association with urine neutrophil gelatinase-associated lipocalin(NGAL)marker in identifying acute tubular necrosis(ATN)in patients with cirrhosis.AIM To assess the reliability of urine NGAL in the detection of ATN in patients with cirrhosis.METHODS We systematically searched MEDLINE and PubMed using keywords including“urine biomarkers”,“NGAL”,“kidney dysfunction”,and“cirrhosis”to identify relevant studies.Data was screened and extracted.Included studies assessed hospitalized cirrhosis patients with AKI using the urine NGAL biomarker.We synthesized the data using diagnostic odds ratio(DOR),comparative and descriptive analyses,and Cochran Mantel-Haenszel(CMH)statistics to evaluate heterogeneity.RESULTS Three thousand seven hundred and one patients with cirrhosis were analyzed from a total of 21 cohort studies.The DOR of 14 of those studies[pooled DOR:22.150,(95%CI:17.58-27.89),P<0.0001]demonstrated a significant association between urine NGAL levels and its identification of ATN.Following stratification by cirrhosis status,heterogeneity was analyzed and showed a significant non-zero correlation between NGAL and AKI(CMH statistic=702.19,P<0.0001).CONCLUSION In patients with cirrhosis,the use of urine NGAL is a reliable biomarker for detecting ATN and identifying the etiology of AKI.展开更多
BACKGROUND Corrosive ingestion remains an important global pathology with high morbidity and mortality.Data on the acute management of adult corrosive injuries from sub-Saharan Africa is scarce,with international inve...BACKGROUND Corrosive ingestion remains an important global pathology with high morbidity and mortality.Data on the acute management of adult corrosive injuries from sub-Saharan Africa is scarce,with international investigative algorithms,relying heavily on computed tomography(CT),having limited availability in this setting.AIM To investigate the corrosive injury spectrum in a low-resource setting and the applicability of parameters for predicting full-thickness(FT)necrosis and mortality.METHODS A retrospective analysis of a prospective corrosive injury registry(March 1,2017–October 31,2023)was performed to include all adult patients with acute corrosive ingestion managed at a single,academic referral centre in Cape Town,South Africa.Patient demographics,corrosive ingestion details,initial investigations,management,and short-term outcomes were described using descriptive statistics while multivariate analysis with receiver operator characteristic area under the curve graphs(ROC AUC)were used to identify factors predictive of FT necrosis and 30-day mortality.RESULTS One-hundred patients were included,with a mean age of 32 years(SD:11.2 years)and a male predominance(65.0%).The majority(73.0%)were intentional suicide attempts.Endoscopy on admission was the most frequent initial investigation performed(95 patients),while only 17 were assessed with CT.Seventeen patients had full thickness necrosis at surgery,of which eleven underwent emergency resection and six were palliated.Thirty-day morbidity and mortality were 27.0%and 14.0%,respectively.Patients with full thickness necrosis and those with an established perforation had a 30-day mortality of 58.8%and 91.0%,respectively.Full thickness necrosis was associated with a cumulative 2-year survival of only 17.6%.Multivariate analyses with ROC AUC showed admission endoscopy findings,CT findings,and blood gas findings(pH,base excess,lactate),to all have significant predictive value for full thickness necrosis,with endoscopy proving to have the best predictive value(AUC 0.850).CT and endoscopy findings were the only factors predictive of early mortality,with CT performing better than endoscopy(AUC 0.798 vs 0.759).CONCLUSION Intentional corrosive injuries result in devastating morbidity and mortality.Locally,early endoscopy remains the mainstay of severity assessment,but referral for CT imaging should be considered especially when blood gas findings are abnormal.展开更多
Osteoarticular complications are common after renal transplantation. The complications may result from the bone condition prior to transplantation or the iatrogenic effects of the treatments administered. These compli...Osteoarticular complications are common after renal transplantation. The complications may result from the bone condition prior to transplantation or the iatrogenic effects of the treatments administered. These complications lead to significant morbidity and mortality, in addition to chronic pain and functional impairment. We report the clinical case of bilateral avascular necrosis (AVN) of the femoral head in a kidney transplant recipient. Clinical Case: 53-year-old male with a history of chronic hypertension. He underwent chronic hemodialysis for 12 months and was treated with Entecavir for chronic hepatitis B. The patient received a kidney transplant from a non-related living donor. Induction therapy included Thymoglobulin along with tapered corticosteroids, reaching a dose of 5 mg/day after 3 months, Mycophenolate mofetil (2 g/day), and Tacrolimus adjusted based on residual levels. There was good recovery of renal graft function. After six months, the patient reported bilateral hip pain and functional impairment of both lower limbs. Pelvic X-rays showed signs suggestive of bilateral AVN of the femoral heads. The diagnosis was confirmed by MRI. The patient underwent right hip drilling and total left hip replacement (THR). A right THR was performed a year later. Conclusion: AVN constitutes a frequent cause of morbidity and mortality after RT. The pathophysiology of osteonecrosis remains complex and multifactorial. We emphasize the importance of conducting a thorough assessment of bone health in patients both before and after RT.展开更多
Scalp necrosis is uncommon in malnourished children,yet temporal catheterization is frequently observed in pediatric hospital settings.The condition is characterized by a black,hard,and unresponsive scalp.Etiologies s...Scalp necrosis is uncommon in malnourished children,yet temporal catheterization is frequently observed in pediatric hospital settings.The condition is characterized by a black,hard,and unresponsive scalp.Etiologies such as temporal arteritis,burns,and Takayasu’s disease,have been proposed.There is a decline in the use of peripheral catheter monitoring in hospitals.War-related food shortages and social instability significantly affect the trauma and risks that undermine the health,social,and psychological well-being of children.This report describes the case of a 5-month-old infant suffering from severe acute malnutrition following the abduction and subsequent release of his mother by armed individuals after one and a half weeks.The infant,who underwent temporal catheterization for medication administration,presented with extensive scalp necrosis.The necrotic tissue was surgically removed,and the malnutrition was successfully treated,resulting in a favorable clinical outcome.The mother received comprehensive mother-child care from a psychologist.展开更多
BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other derma...BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other dermatological conditions.This study aims to investigate these challenges by conducting a comprehensive analysis of a case presenting with PC-ALCL,emphasizing the necessity of accurate differentiation for appropriate management.CASE SUMMARY An 89-year-old female patient with diabetes and hypertension presented with arm and abdominal ulcerated mass lesions.Diagnostic procedures included skin biopsies,histopathological assessments,and immunohistochemistry,complemented by advanced imaging techniques to confirm the diagnosis.The patient’s lesions were determined as PC-ALCL,characterized by necrosis,chronic inflammation,and a distinct immunophenotypic profile,including CD30,CD3,CD4,and EBER,CD56,MUM-1,Ki 67-positive in>80%of tumor cells,CD10,but negative for anaplastic lymphoma kinase,CD5,CD20,PAX-5,Bcl-2,Bcl-6,CD8,and CD15.Recurrence was not reported at the 6-month follow-up.CONCLUSION Accurate PC-ALCL differentiation from similar conditions is crucial for effective management and requires a multidisciplinary approach.展开更多
文摘Frontal osteitis complicated with bone necrosis is rare.In addition,the condition has various etiologies,such as frontal sinusitis,penetrating head injury,postoperative complications after sinus surgery,and hematogenous spread from distant sites.In frontal osteitis,early diagnosis is important,and fistulization of pus in the scalp or on the traumatized forehead may raise the suspicion of osteitis in one of the skull bones.The exclusion of osteonecrosis is such cases is an emergency;hence,a magnetic resonance imaging and a computed tomography scan are required in the absence of skull radiography.Early administration of the appropriate treatment in the immediate post-trauma period ensures effective prevention of frontal osteitis;however,the treatment of bone necrosis involves debridement and antibiotic therapy to prevent fatal intracranial complications.This report presents the case of a 16-year-old female patient who experienced sexual and physical assault that resulted in undetected frontal trauma complicated with frontal osteonecrosis.Thorough clinical examination of the patient was performed,and follow-up and multidisciplinary management enabled the social integration of the patient.
基金Supported by Cancer Sucks,Bixby,Oklahoma Research Grant.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.
基金Supported by the National Natural Science Foundation of China,No.81671600 and No.81241094Natural Science Foundation of Shandong Province,China,No.ZR2016HM13 and No.ZR2023MH066Qingdao Medical and Health Scientific Research Project,China,No.2024-WJKY160.
文摘BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.
文摘BACKGROUND Although acute pancreatitis and walled-off necrosis(WON)are rare complications following aortic surgery,they are serious risk factors for postoperative mortality.Considering the poor general condition of the postoperative patient,more effective and less invasive treatments are favorable.CASE SUMMARY A 67-year-old man was referred to our hospital for the treatment of WON after acute pancreatitis.He had undergone total aortic arch replacement due to aortic arch aneurysm and coronary artery bypass grafting due to angina pectoris 6 weeks prior in another hospital.On the second postoperative day,laboratory data and computed tomography showed that the patient had developed acute pancreatitis.Although conservative management(antibiotics,hydration,etc.)had helped in relieving the symptoms of acute pancreatitis,peripancreatic fluid collection(PFC)persisted,accompanied by duodenal obstruction and vomiting.Contrastenhanced computed tomography showed that the heterogeneous enhancement and fluid collection in the pancreatic body and tail had increased,consistent with walled-off WON.We therefore performed endoscopic ultrasound-guided transluminal drainage for the PFC.As a result,the WON resolved gradually,resulting in improved oral intake.CONCLUSION Acute pancreatitis is a rare gastrointestinal complication following thoracic and thoracoabdominal aortic aneurysm surgery.To the best of our knowledge,this is the first case of WON after aortic arch surgery treated with endoscopic ultrasound-guided transluminal drainage for PFC.
基金supported by a grant from the National Natural Science Foundation of China(82470680).
文摘Background:Infected pancreatic necrosis(IPN)is a highly morbid local complication following necrotizing pancreatitis.Early enteral nutrition has been proven to be effective in preventing IPN.This study aimed to assess the association between the trajectory of prealbumin(PAB)during the early phase of acute pancreatitis(AP)and the incidence of IPN and other clinical outcomes.Methods:This retrospective,dual-centered study screened patients with AP admitted to the Center of Acute Pancreatitis,Jinling Hospital and the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2022.The PAB levels during the first week after admission were collected.The primary outcome was the incidence of IPN within 90 days after AP onset.Group-based trajectory modelling was performed to describe the trajectory of PAB levels over time.A Cox proportional hazard model was used to facilitate the interpretation of the time-varying hazard ratio(HR)between PAB and outcomes.Fine-Gray sub-distribution hazard model was adopted for sensitivity analysis.Results:A total of 373 patients were included,of whom 82(22.0%)were diagnosed with IPN within 90 days.The trajectory model assigned 232 patients to the low-level PAB(L-PAB)group and 141 to the high-level PAB(H-PAB)group.The incidence of 90-day IPN in the L-PAB group was significantly higher than that in the H-PAB group(26.7%vs.14.2%,P=0.005).The multivariate Cox regression model showed that a high PAB trajectory was associated with a lower incidence of IPN(HR=0.52,95%CI:0.30-0.89;P=0.017)after adjustment for potential confounders.In the sensitivity analysis,taking death as a com-peting risk,high PAB trajectory remained significantly associated with a lower incidence of IPN in the Fine-Gray model(HR=0.55,95%CI:0.33-0.92;P=0.022).Conclusions:A high PAB trajectory within the first week of AP was significantly associated with a lower incidence of IPN within 90 days after AP onset.Dynamic monitoring of PAB levels in the early phase of AP may play an important role in stratifying patients at high risk of developing IPN.
基金Medical Science and Technology Disciplinary Reserve Talent Program under the Kunming Municipal Health Science and Technology Talent Cultivation Project(Project No.:2024-SW(Reserve)-45)Health Research Project of the Kunming Municipal Health Commission(Project No.:2023-03-06-012)。
文摘Laparoscopic sleeve gastrectomy(LSG),as an effective treatment for morbid obesity and its metabolic complications,exerts its therapeutic effects by significantly reducing body weight and improving metabolic disorders.Its core mechanisms involve multi-level regulation of free fatty acid(FFA)metabolism and chronic low-grade inflammatory states(represented by tumor necrosis factor-alpha,TNF-α).This paper systematically reviews the direct impact of LSG on FFA dynamics including lipolysis,tissue uptake,and oxidation,as well as the molecular pathways through which it indirectly regulates TNF-αby reducing adipose tissue inflammation,improving intestinal barrier function,and modulating epigenetic modifications such as SCD gene methylation.Postoperatively,FFA and TNF-αform a bidirectional promoting feedback loop.LSG effectively breaks this vicious cycle of mutual promotion between the two under obese conditions by reducing FFA levels and inhibiting TNF-αexpression.Lower FFA levels alleviate inflammatory signal activation,while reduced TNF-αinhibits lipolysis,collectively promoting the restoration of insulin sensitivity.A thorough understanding of these mechanisms provides a theoretical basis for optimizing surgical strategies and developing targeted therapies.
基金Supported by Ministry of Science and Technology,Taiwan,No.MOST 111-2314-B-002-226National Taiwan University Hospital,Hsin-Chu Branch,No.112-BIH017The Liver Disease Prevention and Treatment Research Foundation,Taiwan.
文摘BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.
基金Supported by The Project of Nantong City Health Committee,No.MS2023027 and WKZL2018017The“333”Talent Funding Project of Jiangsu Province,No.BRA2020198+1 种基金The Project of Jiangsu Provincial Health Commission,No.ZD2021059The Youth Research Fund of Nantong Municipal Health Commission,No.QNZ2023027.
文摘BACKGROUND Irreversible transmural intestinal necrosis(ITIN)is associated with high mortality rates in patients with acute occlusive mesenteric ischemia(AOMI).Currently,there are not many studies on the use of dual energy computed tomography(DECT)for evaluating ITIN.AIM To evaluate the diagnostic value of DECT for ITIN in AOMI.METHODS The cases and computed tomography(CT)images of 102 patients with clinically diagnosed AOMI(including 48 ITIN)from January 2012 to January 2022 were retrospectively collected.The CT scans included both multidetector CT and DECT.The raw data from DECT portal-venous phase were reconstructed into 120 kVp mixed energy image,50 keV virtual monoenergetic imaging,and iodine map.Two radiologists independently completed the subjective visual assessment of CT signs related to AOMI.Objective parameters,including the attenuation of the normal and_(lesion)intestinal wall segment(CT50 keV_(lesion),CT_(50 keV normal/lesion))and iodine concentrations(IC_(lesion)and I_(Cnormal/lesion)),were quantified.Furthermore,multivariate logistic regression,receiver operating characteristic curves,and area under the curve(AUC)values were used to evaluate the subjective and objective indicators in predicting ITIN.RESULTS Regarding subjective signs,logistic regression analysis revealed reduced or absent bowel wall enhancement[odds ratio(OR)=5.576,95%confidence interval(CI):1.547-20.093],bowel dilation(OR=11.613,95%CI:3.790-35.586),and parenchymatous organ infarction(OR=4.727,95%CI:1.536-14.551)were independent risk factors for the ITIN.CT subjective signs had a high diagnostic efficacy for ITIN(AUC=0.853).The two DECT objective parameters also exhibited excellent diagnostic value for ITIN,with an AUC of 0.79,a cut-off value of CT50 keV normal/_(lesion)=2.81,and an AUC of 0.777 with a cut-off value of I_(Cnormal/lesion)=2.39.The Delong test showed that there was no significant difference in the efficacy of subjective CT signs and objective DECT parameters(P>0.05).Importantly,we observed that I_(Cnormal/lesion)combined with subjective signs(bowel dilation and parenchymatous organ infarction)had the highest predictive performance(AUC=0.894),sensitivity(100%),and specificity(70.83%),which was statistically different from the AUC of CT subjective signs(P=0.017).CONCLUSION I_(Cnormal/lesion)(DECT-based features)combined with CT subjective signs(bowel dilatation and parenchymatous organ infarction)showed favorable predictive performance for ITIN in AOMI,which may help clinicians develop timely treatment strategies.
基金supported by the Natural Science Foundation of China(81873325)the State Administration of Traditional Chinese Medicine of Zhejiang Province(2021ZZ014).
文摘The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated that GC exacerbates the oxidative stress(OS)microenvironment via promoting nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)expression in human,rat,and mesenchymal stem cells(MSCs)samples,thus generating excessive reactive oxygen species(ROS),leading to increased apoptosis and unbalanced osteolipogenic differentiation.Furthermore,computational docking results revealed that AMY could bind specifically to the predicted binding sites of NOX4.Additionally,AMY ameliorated the OS microenvironment of MSCs via decreasing NOX4 expression and inhibiting NOX4/ROS/p38MAPK signaling,thereby reversing the GC-induced apoptosis and imbalanced osteolipogenic differentiation,and ultimately alleviating GANFH.In summary,we demonstrated for the first time that AMY attenuated apoptosis and maintained osteolipogenic differentiation balance in MSCs via specifically targeting NOX4,inhibiting NOX4/ROS/p38MAPK signaling,thereby treating GANFH.
基金supported the National Natural Science Foundation of China,No.81974178(to CD).
文摘Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.
文摘Approximately 20%-30%of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis(IPN),a highly morbid and potentially lethal complication.Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes.In the past two decades,several markers and predictive tools have been proposed and evaluated for this purpose.Conventional biomarkers like C-reactive protein,procalcitonin,lymphocyte count,interleukin-6,and interleukin-8,and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN.On the other hand,scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested,and the results showed that they may provide better accuracy.For early prevention of IPN,several new therapies were tested,including early enteral nutrition,anti-biotics,probiotics,immune enhancement,etc.,but the results varied.Taken together,several evidence-supported predictive markers and scoring systems are readily available for predicting IPN.However,effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition.In this editorial,we summarize evidence concerning early prediction and prevention of IPN,providing insights into future practice and study design.A more homo-geneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN,thereby achieving individualized treatment.
基金National Key R&D Program of China:Cooperating Studies on Measurement Technologies of Human Phenome and Crossscale Correlation of Phenotypic Data(No.2020YFE0201600)National Nature Science Foundation:Study on LncRNA-CCDC18-AS1 Mediated Osteosarcoma Occurrence by Activating YAP/TAZ and Tumor Microenvironment M2 TAM-dependent Lung Metastasis,and Efficacy/mechanism of Removing Blood Stasis/clearing heat/eliminating Toxic Material Principle(No.81973877)+2 种基金Mechanism Study on m6A Methyltransferase RBM15 Mediated YAP Epigenetic Modification to Promote Osteosarcoma Lung Metastasis through Lymphatic System and Management with Qichong Powder(No.82174408)Shanghai Collaborative Innovation Center of Industrial Transformation of Hospital TCM Preparation:Preclinical Study on the Treatment of Osteosarcoma with Qingre Jiedu GranulesResearch Projects within Budget of Shanghai University of Traditional Chinese Medicine:the Research on the Mechanism of the HIPK3 Activation of Wnt/β-catenin Induction the Osteosarcoma and the Intervention of Banmao Decoction(No.2021LK047)。
文摘OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.METHODS:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays.The morphology of cancer cells was observed with inverted phase contrast microscope.The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays.The expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting assay.RESULTS:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells.The synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.CONCLUSION:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.
基金supported by the National Natural Science Foundation of China,Nos.82102295(to WG),82071339(to LG),82001119(to JH),and 81901994(to BZ).
文摘Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.
文摘BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.
基金Supported by Department of Health of Zhejiang Province,No.2019-KY1-001-138Zhejiang Provincial Natural Science Foundatio,No.LTGY24H160016。
文摘BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.
文摘BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be used to assess the type of AKI and the severity of the disease.We performed a systematic review with metaanalysis to evaluate the association with urine neutrophil gelatinase-associated lipocalin(NGAL)marker in identifying acute tubular necrosis(ATN)in patients with cirrhosis.AIM To assess the reliability of urine NGAL in the detection of ATN in patients with cirrhosis.METHODS We systematically searched MEDLINE and PubMed using keywords including“urine biomarkers”,“NGAL”,“kidney dysfunction”,and“cirrhosis”to identify relevant studies.Data was screened and extracted.Included studies assessed hospitalized cirrhosis patients with AKI using the urine NGAL biomarker.We synthesized the data using diagnostic odds ratio(DOR),comparative and descriptive analyses,and Cochran Mantel-Haenszel(CMH)statistics to evaluate heterogeneity.RESULTS Three thousand seven hundred and one patients with cirrhosis were analyzed from a total of 21 cohort studies.The DOR of 14 of those studies[pooled DOR:22.150,(95%CI:17.58-27.89),P<0.0001]demonstrated a significant association between urine NGAL levels and its identification of ATN.Following stratification by cirrhosis status,heterogeneity was analyzed and showed a significant non-zero correlation between NGAL and AKI(CMH statistic=702.19,P<0.0001).CONCLUSION In patients with cirrhosis,the use of urine NGAL is a reliable biomarker for detecting ATN and identifying the etiology of AKI.
文摘BACKGROUND Corrosive ingestion remains an important global pathology with high morbidity and mortality.Data on the acute management of adult corrosive injuries from sub-Saharan Africa is scarce,with international investigative algorithms,relying heavily on computed tomography(CT),having limited availability in this setting.AIM To investigate the corrosive injury spectrum in a low-resource setting and the applicability of parameters for predicting full-thickness(FT)necrosis and mortality.METHODS A retrospective analysis of a prospective corrosive injury registry(March 1,2017–October 31,2023)was performed to include all adult patients with acute corrosive ingestion managed at a single,academic referral centre in Cape Town,South Africa.Patient demographics,corrosive ingestion details,initial investigations,management,and short-term outcomes were described using descriptive statistics while multivariate analysis with receiver operator characteristic area under the curve graphs(ROC AUC)were used to identify factors predictive of FT necrosis and 30-day mortality.RESULTS One-hundred patients were included,with a mean age of 32 years(SD:11.2 years)and a male predominance(65.0%).The majority(73.0%)were intentional suicide attempts.Endoscopy on admission was the most frequent initial investigation performed(95 patients),while only 17 were assessed with CT.Seventeen patients had full thickness necrosis at surgery,of which eleven underwent emergency resection and six were palliated.Thirty-day morbidity and mortality were 27.0%and 14.0%,respectively.Patients with full thickness necrosis and those with an established perforation had a 30-day mortality of 58.8%and 91.0%,respectively.Full thickness necrosis was associated with a cumulative 2-year survival of only 17.6%.Multivariate analyses with ROC AUC showed admission endoscopy findings,CT findings,and blood gas findings(pH,base excess,lactate),to all have significant predictive value for full thickness necrosis,with endoscopy proving to have the best predictive value(AUC 0.850).CT and endoscopy findings were the only factors predictive of early mortality,with CT performing better than endoscopy(AUC 0.798 vs 0.759).CONCLUSION Intentional corrosive injuries result in devastating morbidity and mortality.Locally,early endoscopy remains the mainstay of severity assessment,but referral for CT imaging should be considered especially when blood gas findings are abnormal.
文摘Osteoarticular complications are common after renal transplantation. The complications may result from the bone condition prior to transplantation or the iatrogenic effects of the treatments administered. These complications lead to significant morbidity and mortality, in addition to chronic pain and functional impairment. We report the clinical case of bilateral avascular necrosis (AVN) of the femoral head in a kidney transplant recipient. Clinical Case: 53-year-old male with a history of chronic hypertension. He underwent chronic hemodialysis for 12 months and was treated with Entecavir for chronic hepatitis B. The patient received a kidney transplant from a non-related living donor. Induction therapy included Thymoglobulin along with tapered corticosteroids, reaching a dose of 5 mg/day after 3 months, Mycophenolate mofetil (2 g/day), and Tacrolimus adjusted based on residual levels. There was good recovery of renal graft function. After six months, the patient reported bilateral hip pain and functional impairment of both lower limbs. Pelvic X-rays showed signs suggestive of bilateral AVN of the femoral heads. The diagnosis was confirmed by MRI. The patient underwent right hip drilling and total left hip replacement (THR). A right THR was performed a year later. Conclusion: AVN constitutes a frequent cause of morbidity and mortality after RT. The pathophysiology of osteonecrosis remains complex and multifactorial. We emphasize the importance of conducting a thorough assessment of bone health in patients both before and after RT.
文摘Scalp necrosis is uncommon in malnourished children,yet temporal catheterization is frequently observed in pediatric hospital settings.The condition is characterized by a black,hard,and unresponsive scalp.Etiologies such as temporal arteritis,burns,and Takayasu’s disease,have been proposed.There is a decline in the use of peripheral catheter monitoring in hospitals.War-related food shortages and social instability significantly affect the trauma and risks that undermine the health,social,and psychological well-being of children.This report describes the case of a 5-month-old infant suffering from severe acute malnutrition following the abduction and subsequent release of his mother by armed individuals after one and a half weeks.The infant,who underwent temporal catheterization for medication administration,presented with extensive scalp necrosis.The necrotic tissue was surgically removed,and the malnutrition was successfully treated,resulting in a favorable clinical outcome.The mother received comprehensive mother-child care from a psychologist.
文摘BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other dermatological conditions.This study aims to investigate these challenges by conducting a comprehensive analysis of a case presenting with PC-ALCL,emphasizing the necessity of accurate differentiation for appropriate management.CASE SUMMARY An 89-year-old female patient with diabetes and hypertension presented with arm and abdominal ulcerated mass lesions.Diagnostic procedures included skin biopsies,histopathological assessments,and immunohistochemistry,complemented by advanced imaging techniques to confirm the diagnosis.The patient’s lesions were determined as PC-ALCL,characterized by necrosis,chronic inflammation,and a distinct immunophenotypic profile,including CD30,CD3,CD4,and EBER,CD56,MUM-1,Ki 67-positive in>80%of tumor cells,CD10,but negative for anaplastic lymphoma kinase,CD5,CD20,PAX-5,Bcl-2,Bcl-6,CD8,and CD15.Recurrence was not reported at the 6-month follow-up.CONCLUSION Accurate PC-ALCL differentiation from similar conditions is crucial for effective management and requires a multidisciplinary approach.
